"We Murder to Dissect"

Star Trek aficionados all share a certain fondness for the transporter, the device that allowed the intrepid crew of the Enterprise to plunk down on various planets without benefit of spacecraft. The premise of the transporter was that Captain Kirk, say, could be disassembled into tiny transportable packets, which would then be reassembled at the destination: same Captain Kirk, new location. When functioning correctly, the transporter could, essentially, deconstruct him and then put him back together again—no harm done. I cite this fictional device because it serves as an excellent emblem for the fallacies of reductionism—fallacies that Stephen Rothman seems eager to explore in Lessons from the Living Cell, even as the book displays reductionist leanings of its own.

Rothman examines some of the influential assumptions that have animated much of biology over the past 50 years. Simply stated, biological systems—organisms—have been seen as elaborate machines, assembled from a large number of smaller interacting components. This Cartesian perspective implies a specific methodological imperative: To understand the whole, you must understand the parts. To examine biological phenomena, scientists have largely worked toward the identification of constituent parts, as this book demonstrates. All along, we are assured, the separate understanding of each of the parts will add up to an understanding of the system as a whole.

Does this approach work? Stephen Rothman thinks not. Most of us would argue that it has been immensely successful in biology and has perhaps been responsible for the emergence of biology as the premier science of our time. But Rothman would strongly argue with the path used to attain such success. He contends that the reductionist approach, despite some excellent results, ultimately blinds us to important and obvious conclusions about the living world. The preference for reductionist explanation, he believes, distorts the way scientists view and understand the natural world.

This book, as its subtitle indicates, means to break the grip of reductionism on cell biology. The author uses his own research as a case in point. He has spent a good deal of his career advocating a minority view on how proteins are transported within and secreted out of the cell. The prevailing model argues that specific proteins are shuttled around to their destinations, both within and outside the cell, in enclosed vesicles. But to Rothman, the vesicle model lives simply because of the misguided commitment of its advocates to a reductionist approach. The model has survived, he contends, because scientists insist on grinding up cells in order to understand them, which has resulted in a wholly unsupported picture of cellular traffic. If the cell were simply allowed to speak, argues Rothman, it would not speak of vesicles.

This book obviously means to call into question the validity of the vesicle theory. More interesting, however, is the author's attempt to indict the reductionist approach as the cause for dogmatic adherence to the vesicle model. At this point in Rothman's argument, the book falters, yet for an interesting reason: In fingering reductionism, Rothman has picked the wrong suspect. In effect, this tale of vesicles is not about the limits of reductionism, but about the limits of Karl Popper's oft-repeated claim that a real scientific hypothesis must be falsifiable.

Rothman details one instance after another of results that appear to contradict the vesicle model yet fail to dislodge it from the minds of cell biologists. He bemoans the fact that inductive logic takes precedence over deductive statements: "The central point is that models and theories arrived at inductively represent merely the beginning of the search for understanding. . . . Deductively constructed hypotheses serve the purpose of assessing the correctness of inductively generated models . . . against the properties of nature." This type of theory can galvanize an undergraduate seminar on the philosophy of science, but it is a long way from the grinding, grunting, messy work being done in the trenches.

Ultimately, Lessons from the Living Cell is a story about the many extrascientific forces that shape a field: personalities, politics, allegiances, editors, funding agencies and dumb luck. These forces, which underscore that science is simply one more human intellectual undertaking, are at play for reductionists and nonreductionists alike. Ironically, the strongest support for Rothman's minority view comes from a deeply reductive insight about the physical chemistry of biological membranes and membrane pores, which we now realize can and do allow the passage of large charged molecules into and out of the cell, making possible the diffusion of newly synthesized proteins without the assistance of vesicles. The book is thus more about the deeply human character of the scientific enterprise than about the failures of reductionism.

It is unfortunate that Rothman does not make a stronger case—particularly now, when the major reductionist initiatives are bearing fruit and the limitations of the approach are becoming most apparent. The Human Genome Project, for example, might be a complete description of human DNA, but it is not a complete explanation of what makes a human being.

This distinction between description and explanation is well understood but has been somewhat lost in the enthusiasm for all things genomic. Biology is periodically infatuated with a sort of reflexive reductionism that argues that anything in biology worth knowing can be derived from a DNA sequence. As with all infatuations, it is an illusion. That wisdom and insight would tumble from complete lists of ordered nucleotides was easier to maintain when whole genome sequences were unobtainable. Now sequencing has become routine and inexpensive, and several new complete genomes appear every year. Valuable and surprising as these data are, insight is still a rare commodity, still dependent on human imagination and persistence.

The real danger turns out to come not from the reductionist approach, but rather from conflating simpler parts with smaller parts. Reductionism works best when complex phenomena at one level are carefully disassembled into simpler components at the same or adjacent levels. But driven largely by the siren song of molecular biology, we reduce complex biological problems to their smallest components: genes and sequences. We are finding out the hard way that answers are not always embedded in DNA and that many questions lose coherence when recast at the wrong level.

As Rothman argues in the early part of this book, much that matters in biology—evolutionary history, nonlinear interactions, emergent features, organization—cannot be understood solely by examining sequences and molecules. More than 200 years ago, Wordsworth sounded a useful warning in his poem "The Tables Turned":

Sweet is the lore which Nature brings;
Our meddling intellect
Mis-shapes the beauteous forms of things:--
We murder to dissect.

If we want to understand the world, perhaps it is true that we must first deconstruct it. But an unexamined belief in the intellectual power of reductionism, a belief that has achieved quasi-religious status in biology, may indeed limit the creative power of insight, the very power that allows us to interpret what we dissect.